A Future Without Hepatitis C?

The Liver Meeting 2014: American Association for the Study of Liver Diseases (AASLD)

William F. Balistreri, MD


December 16, 2014

In This Article


Several presentations reported the safety and efficacy of a new combination—SOF with GS-5816—an investigational inhibitor of the HCV NS5A protein with picomolar antiviral activity across all HCV genotypes, including patients with genotype 3. This is an important advance because options for the difficult-to-treat genotype 3 infection are limited; the only currently available all-oral regimen requires 24-week treatment that includes RBV.

Tran and colleagues[9] reported the final results from a phase 2 study that evaluated SOF/GS-5816 with or without RBV administration in treatment-naive genotype 1-6 patients without cirrhosis. SOF/GS-5816 (100 mg) for 8 or 12 weeks was well tolerated with a low incidence of treatment discontinuation and adverse events, and high SVR12 rates were achieved. This study demonstrates that coadministration of SOF with GS-5816 and without RBV is an appropriate regimen that should be further evaluated in phase 3 studies.

Pianko and colleagues[10] reported that high SVR12 rates were achieved in treatment-experienced patients with genotype 1 or 3 infection with or without cirrhosis following coadministration of SOF (400 mg) with GS-5816 (100 mg) for 12 weeks without RBV. SOF and GS-5816 were well tolerated, with a low incidence of treatment discontinuation and adverse events.

Gane and colleagues[11] assessed whether the SOF/GS-5816 regimen would be effective for genotype 3 patients when administered for a shorter (8-week) duration. In 104 treatment-naive, noncirrhotic patients, SOF/GS-5816 (25 mg or 100 mg) for 8 weeks, with or without RBV, resulted in high rates (88%-100%) of SVR12. Treatment was well tolerated, with no identified safety signal related to SOF or GS-5816.

The combination of SOF and GS-5816 for 12 weeks has high efficacy in treatment-naive and treatment-experienced genotype 1-6 patients without cirrhosis.

MK-5172 (Grazoprevir) and MK-8742 (Elbasvir)

Lawitz and colleagues[12] assessed the efficacy, safety, and effective treatment duration of MK-5172 in combination with MK-8742 with or without RBV in patients with genotype 1 infection and baseline characteristics of poor response (either cirrhosis or previous null response to peg-IFN/RBV). This aggressive regimen achieved high rates of efficacy following as few as 4 weeks of treatment. Neither RBV nor extension of treatment duration from 12 to 18 weeks was needed to achieve SVR12 in a high proportion of patients.

Sulkowski and colleagues[13] also assessed the efficacy, safety, and durability of response to once-daily MK-5172 and MK-8742 combined with RBV in treatment-naive, noncirrhotic genotype 1 HCV monoinfected and HIV/HCV coinfected patients. The SVR12 rates for mono- and coinfected patients treated for 12 weeks with or without RBV were 95% and 93%, respectively.


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